Curr Diab Rep (2014) 14:457 DOI 10.1007/s11892-013-0457-x

HOSPITAL MANAGEMENT OF DIABETES (G UMPIERREZ, SECTION EDITOR)

Inpatient Management of Women with Gestational and Pregestational Diabetes in Pregnancy Etoi A. Garrison & Shubhada Jagasia

Published online: 11 January 2014 # Springer Science+Business Media New York 2014

Abstract For women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM), poor maternal glycemic control can significantly increase maternal and fetal risk for adverse outcomes. Outpatient medical and nutrition therapy is recommended for all women with diabetes in order to facilitate euglycemia during the antepartum period. Despite intensive outpatient therapy, women with diabetes often require inpatient diabetes management prior to delivery as maternal hyperglycemia can significantly increase neonatal risk of hypoglycemia. Consensus guidelines recommend maternal glucose range of 80–110 mg/dL in labor. The most optimal inpatient strategies for the prevention of hyperglycemia and hypoglycemia proximate to delivery remain unclear and will depend upon factors such as maternal diabetes diagnosis, her baseline insulin resistance, duration and route of delivery etc. Low dose intravenous insulin and dextrose protocols are necessary to achieve optimal predelivery glycemic control for women with T1DM and T2DM. For most with GDM however, euglycemia can be maintained without intravenous insulin. Women treated with a subcutaneous insulin pump during the antepartum period represent a unique challenge to labor and delivery staff. Strategies for self-managed subcutaneous insulin infusion (CSII) use prior to delivery require intensive education and coordination of care with the labor team in order to maintain patient safety. Hospitalization is recommended for most women with diabetes prior to delivery and in the postpartum period despite appropriate outpatient glycemic control. Women with poorly controlled

This article is part of the Topical Collection on Hospital Management of Diabetes E. A. Garrison : S. Jagasia (*) Vanderbilt University Medical Center, 8210 Medical Center East South Tower, 1215 21st Avenue South, Nashville, TN 37232-8148, USA e-mail: [email protected]

diabetes in any trimester have an increased baseline maternal and fetal risk for adverse outcomes. Common indications for antepartum hospitalization of these women include failed outpatient therapy and/or diabetic ketoacidosis (DKA). Inpatient management of DKA is a significant cause of maternal and fetal morbidity and remains a common indication for hospitalization of the pregnant woman with diabetes. Changes in maternal physiology increase insulin resistance and the risk for DKA. A systematic approach to its management will be reviewed. Keywords Type 1 diabetes . Type 2 diabetes . Gestational diabetes . Pregestational diabetes . Labor . Intrapartum . Postpartum . Intravenous insulin . Insulin pump . U-500 . Diabetic ketoacidosis . Pregnancy

Introduction Good antenatal care, frequent glucose self-monitoring, and medical-nutritional therapy are associated with improved glycemic control and a reduction in the risk of adverse maternal and neonatal outcomes for women with diabetes in pregnancy [1]. Inpatient management of diabetes during pregnancy can present unique challenges for both the patient and her obstetrician. Despite appropriate outpatient antepartum care, maternal hyperglycemia in labor can increase the risk for neonatal hypoglycemia [2–4, 5•]. For women with significant insulin resistance who are poorly controlled and remote from delivery, antepartum hospitalization may be required for optimization of therapy and patient education. DKA is associated with significant maternal/fetal morbidity and mortality. The increasing insulin resistance of pregnancy places women with T1DM and T2DM at significant risk for DKA. Rare cases of DKA for women with GDM have also been reported. This paper will review inpatient management strategies for women

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with diabetes who require hospitalization for (1) intrapartum and postpartum care, (2) U-500 regular insulin administration due to poor glycemic control, and (3) DKA.

Intrapartum Diabetes Management The goals of intrapartum management for women with diabetes in pregnancy are to prevent maternal hyperglycemia, minimize the risk of maternal hypoglycemia, and optimize short term neonatal outcome [1]. Despite good antepartum glycemic control, there is a positive correlation between the risk of neonatal hypoglycemia postdelivery and maternal glycemia in labor [4, 6]. Intravenous insulin and dextrose protocols used to maintain euglycemia for the laboring patient are associated with a significant reduction in the risk of neonatal hypoglycemia for women with pregestational and gestational diabetes [6–8].

Fetal Risk and Maternal Intrapartum Glucose Targets It has been estimated that up to 50 % of infants born to diabetic mothers will experience hypoglycemia after birth [4, 9]. Clinical consequences for the neonate depend upon the severity and duration of hypoglycemia, the underlying etiology, and the need for transfer to the ICU [9]. Neonatal hypoglycemia is more likely to occur for fetuses that are born to diabetic women with poor glycemic control and/or are macrosomic [2–4, 5•]. Infants of poorly controlled diabetic mothers can develop islet cell hyperplasia and baseline hyperinsulinemia in utero during the antepartum period. They are at risk for clinically significant neonatal hypoglycemia when maternal glucose transfer ceases with delivery [2–4, 5•]. The maintenance of euglycemia for diabetic women in labor has been demonstrated to reduce but cannot eliminate neonatal hypoglycemia particularly for those fetuses with diabetic fetopathy in utero due to poor antepartum glycemic control [10]. Predelivery diabetes management is influenced by maternal diabetes diagnosis, baseline insulin sensitivity, the progress of labor, and its duration. Women with T1DM require administration of glucose and insulin during prolonged labor in order to prevent ketosis. Those with GDM and T2DM have insulin requirements that vary depending upon the duration of maternal disease, stage of labor, antepartum glycemic control, and baseline insulin resistance. Insulin requirements for women with GDM may be influenced by gestational age at diagnosis and her risk for overt T2DM. Historically, initial published reports either described the use of an insulin protocol for type 1 diabetics in labor or included a mixed population of women with both GDM and T1 or T2DM [6, 10–14]. Less is known regarding the comparative efficacy of these protocols for each population separately.

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Several intravenous insulin/glucose protocols have been published for the maintenance of euglycemia during labor. There are few, if any, randomized controlled trials available as best evidence to support one management approach over the others. A target glucose range of 70–110 mg/dL (3.6– 6.1 mmol/L) in labor for both gestational and pregestational diabetics is supported by the American College of Obstetrics and Gynecology (ACOG) and the American College of Endocrinology (ACE) [1, 15]. Several studies suggest that higher levels of maternal glycemia [glucose ≥126 mg/dL (7 mmol/L)] may be safely permitted during labor without increasing neonatal hypoglycemia risk. In a retrospective evaluation of 107 women with T1DM in labor by Taylor et al 46 % of the neonates had persistent hypoglycemia (glucose 8 mmol/L (144 mg/dL) and neonatal hypoglycemia. These results were confirmed in other studies and suggest that maternal glycemia 15–30 mg/ dL above the consensus threshold of 110 mg/dL may be permissible without significantly increasing neonatal risk [16, 17]. These studies further suggest that neonatal hypoglycemia may occur despite euglycemia in labor. The correlation between neonatal hypoglycemia, intrapartum maternal glycemia, and markers of antepartum maternal glycemic control require further study. The demands of labor necessitate glucose as an energy source. Oral intake during labor is restricted at many institutions due to maternal aspiration risk. Women with T1DM require glucose supplementation in order to keep capillary glucose values within target range and reduce the risk for ketosis. In the latent phase of labor, women with T2DM and GDM may have sufficient glycogen stores to keep capillary glucose >70 mg/dL without supplemental dextrose solutions. Glucose requirements increase, however, with prolonged labor induction, during the active phase of labor, and with maternal pushing [2]. Several excellent glucose/insulin infusion protocols have been published [1, 2, 7, 18, 19•]. Figure 1 depicts elements of the computerized insulin infusion protocol utilized at our institution. This protocol is one of several options available to the practitioner for glycemic control in labor and generates insulin infusion rates that are comparable with those identified in protocols proposed by ACOG and the ADA Technical Reviews and Consensus Recommendations for Care [1, 18]. The insulin protocol used for our obstetric population was adopted in 2010 due to its integration with a point of care based electronic order entry system and is a modification of previously published protocols first utilized in critically ill patients at our institution [20–22]. A comparative analysis of

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Fig. 1 Screen view of computerized intravenous insulin therapy protocol. If maternal glucose is >110 mg/dL on 2 separate occasions, intravenous insulin is ordered as detailed above. A target glucose range of 80– 110 mg/dL is set for all laboring obstetric patients. D5 Normal saline is ordered at 125 cc/h for maintenance fluid if not previously ordered. The computer calculates an insulin drip rate using the following formula: insulin dose (units/hour)=(current glucose (mg/dL) – 60) x multiplier. The multiplier is set at 0.03 but can be d by 0.01 or decreased by 0.01 to 0.02 depending upon subsequent glucose values. An initial glucose value

of 115 would trigger an insulin drip rate of 1.7 units/hr. Nurses enter hourly capillary glucose values into a separate “dose titration page” and the computer algorithm will recommend a modification of the drip rate hourly as indicated to keep glucose within target range. The nurse will either accept or speak with the ordering physician to modify the drip rate based upon the patient’s clinical status. The program saves all capillary glucose values and modifications to the insulin drip rate in the electronic medical record

maternal and fetal outcomes for pregestational and gestational diabetic women will be necessary in order to determine the benefits and limitations of a computer based intravenous insulin protocol compared with the traditional paper-based intravenous insulin algorithms currently available. For women with GDM who are diet controlled during the antepartum period, delivery can occur without the need for intravenous insulin. Up to 65 % of women with GDM who have a fasting glucose≤95 mg/dL at diagnosis can achieve optimal antepartum glycemic control with nutrition alone and as such are at low risk for hyperglycemia in labor [19•, 23]. Flores-Le Roux performed a prospective observational study of 129 women with GDM in labor. Eighty-six percent of study participants had capillary glucose values within target range for their institution (3.3 compared with 7.2 mmol/L) or (59.6 compared with 129.6 mg/dL) and did not require insulin [19•].

A maternal glucose target of 7.2 mmol/L (129.6 mg/dL) was selected as the upper limit of normal for this population based upon prior studies that failed to identify neonatal hypoglycemia below this threshold [7, 17, 24, 25]. Maintaining euglycemia in labor for women with GDM may also be possible without insulin by rotating dextrose and nondextrose containing solutions [16, 26]. Additional research is needed for women with GDM in order to identify an evidence based protocol that will facilitate maternal glycemic control, limit insulin use when not indicated, and reduce the risk of neonatal hypoglycemia. Patients with diabetes in labor who require intravenous insulin are at risk for hypoglycemia if glucose administration is insufficient for maternal demand. Prompt recognition and management of hypoglycemia are important in order to minimize provider error and maternal/fetal risk. Baseline serum glucose levels are 20 % lower in pregnancy compared with the

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nonpregnant state and as such, women with diabetes are at significant risk for symptomatic and asymptomatic hypoglycemia [27]. The management of hypoglycemia in pregnancy is complicated by lack of consensus regarding its definition. The ADA and The Endocrine Society define hypoglycemia as plasma glucose less than 70 mg/dL [28••]. In pregnancy, ACOG and others report fasting glucose of 60 mg/dL to be the lower end of normal range, with mild hypoglycemia defined as a glucose

Inpatient management of women with gestational and pregestational diabetes in pregnancy.

For women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM), poor maternal glycemic control can significantly increa...
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